Chaperone-Directed Ribosome Repair after Oxidative Damage

Abstract

Reactive oxygen species are ubiquitous in cells, where they damage RNA and protein. While relief mechanisms, including effects on translation, have been described, whether ribosomes are functionally compromised by oxidation, and how this damage is mitigated, remains unknown. Here we show that cysteines in ribosomal proteins, including Rps26, are readily oxidized and rendered non-functional, which is exacerbated when yeast are exposed to H2O2. Oxidized Rps26 is released from ribosomes by its chaperone Tsr2, which allows for repair of the damaged ribosomes with newly made Rps26. Ribosomes containing damaged Rpl10 or Rpl23 are similarly repaired by their chaperones, Sqt1 and Bcp1. Ablation of this pathway impairs growth, which is exacerbated under oxidative stress. These findings reveal a novel mechanism for chaperone-mediated ribosome repair with implications for aging and health.

The 3’-untranslated regions of yeast ribosomal protein mRNAs determine paralog incorporation into ribosomes and recruit factors necessary for specialized functions

“…As ribosome heterogeneity resulting from rRNA or RP modifications can also occur after ribosome biogenesis, heterogeneity that arises from paralog usage alone should be easier to examine. This is because assembled ribosomes are likely to be relatively stable, though ribosome repair pathways might potentially contribute to heterogeneity 28 .…”